Recent research on central cardiovascular control indicates the existence of a population of neurons in the lateral medullary reticular formation that provides a final common pathway conveying the excitatory drive to the spinal sympathetic nucleus that is critical for the maintenance of basal sympathetic tone. As described in the proposal, the characterization of these neurons will provide new information on the central neural mechanisms underlying the sympathetic control of blood pressure. The proposed studies will focus on the hypothesis that neurons in the rostral ventrolateral medulla (RVL) that contain the adrenaline-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT) mediate the tonic bulbospinal excitation of sympathetic preganglionic neurons (SPN) necessary for the support of resting blood pressure. Extracellular recording and antidromic activation techniques are combined with baroreceptor reflex activation and computer-aided analysis to identify sympathoexcitatory neurons in RVL that project to the sympathetic intermediolateral nucleus. Immunocytochemical staining is used to determine the proximity of the recording sites of these neurons to the locations of neurons containing PNMT (C1 cell group). Additional experiments are designed to examine (1) the baroreceptor reflex pathway providing an inhibitory control of the activity of these cells and (2) the activation of RVL sympathetic neurons from hypothalamic pressor sites. Microiontophoretic application of antagonist drugs will be used to classify the transmitter system(s) mediating the effects of RVL activation on the activity of SPNs. Together these data would not only increase our knowledge of the basic neural mechanisms involved in central blood pressure regulation, they might also provide a basis for (1) the evaluation of the role of altered neural function in hypertensive disease and (2) the design of pharmacologic approaches to antihypertensive therapy. The former possibility is tested in a final series of experiments to determine if the sympathetic hyperactivity of the spontaneously hypertensive rat is associated with increased activity of the sympathoexcitatory neurons in the C1 region of the RVL.